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Biomedical subjects

Michael H Smith

Publications and source records attributed to Michael H Smith.

7 recordsLinked to original sources

Independent occurrences of multiple repeats in the control region of mitochondrial DNA of white-tailed deer.

Deer in the genera Mazama and Odocoileus generally have two copies of a 75-base-pair (bp) repeat in the left domain of the control region of the mitochondrial DNA (mtDNA). Phylogenetic analyses further suggest an ancient origin for the duplication supporting a previously stated contention that this event occurred before the separation of Mazama and Odocoileus. However, white-tailed deer (Odocoileus virginianus) had three or four copies of a 75-bp repeat in the control region of their mtDNA in 7.8% of the individuals analyzed, and all of these animals were from the coastal plain of the southeastern United States. When copy 3 is present, it is very similar in sequence to copy 2, but variation suggests that copy 3 probably evolved multiple times from copy 2. The pattern of phylogenetic clustering of the haplotypes from across the coastal plain also suggests that phenotypes with three or four copies of the repeat have originated multiple times. The 44 observed haplotypes showed strong spatial subdivision across the area with subpopulations frequently showing complete shifts in haplotype frequencies from others taken from nearby areas. Many of the subpopulations right along the coast or on adjacent barrier islands have a limited number of haplotypes as would occur in populations undergoing drift because of small numbers of breeding females and limited female dispersal.

Animals↗

Genetics of cattails in radioactively contaminated areas around Chornobyl.

Research on populations from radioactively contaminated areas around Chornobyl has produced ambiguous results for the presence of radiation effects. More studies are needed to provide information on whether radiation exposure at Chornobyl significantly affected genetic diversity in natural populations of various taxa. Eleven and nine variable microsatellite loci were used to test for differences in genetic diversity between reference and Chornobyl populations of two cattail species (Typha angustifolia and Typha latifolia, respectively) from Ukraine. Our purpose was to determine whether radiation had a significant impact on genetic diversities of the Chornobyl Typha populations, or if their genetic composition might be better explained by species demography and/or changes in population dynamics, mainly in sexual and asexual reproduction. Populations closest to the reactor had increased genetic diversities and high number of genets, which likely were due to factors other than radiation including increased gene flow among Chornobyl populations, enhanced sexual reproduction within populations, and/or origin of the genets from seed bank. Both Typha species also demonstrated small but significant effects associated with latitude, geographical regions, and watersheds. Typha's demography in Ukraine possibly varies with these three factors, and the small difference between Chornobyl and reference populations of T. latifolia detected after partitioning the total genetic variance between them is probably due primarily to these factors. However, the positive correlations of several genetic characteristics with radionuclide concentrations suggest that radiation may have also affected genetics of Chornobyl Typha populations but much less than was expected considering massive contamination of the Chornobyl area.

Alleles↗

High levels of fluctuating asymmetry in populations of Apodemus flavicollis from the most contaminated areas in Chornobyl.

Random deviations from the perfect symmetry of normally bilaterally symmetrical characters for an individual with a given genotype occur during individual development due to the influence of multiple environmental factors. Fluctuating asymmetry (FA) is often used as a measure of developmental instability, and can be estimated as the variance of the distribution of differences between the left and right sides. We addressed the question of whether levels of FA were elevated in radioactively contaminated populations living around Chornobyl compared to those in reference populations of the yellow-necked mouse (Apodemus flavicollis). In addition, we studied amounts of directional asymmetry (DA) when one side is larger than the other on average. There was a significant difference among populations, including reference populations, in the amount of both FA and DA. A higher level of FA was documented for the contaminated populations in close proximity to the failed Chornobyl reactor for both the asymmetry of size and shape. The FAs of size and shape were highest in populations from the most contaminated locations in the Chornobyl exclusion zone. Although the directional asymmetry of shape was also highest in the contaminated populations, it was not significantly different from those in most of the reference populations. Populations from less contaminated areas inside the Chornobyl exclusion zone did not express FA values different from those of the reference populations outside the affected area. FA of skulls of A. flavicollis may indicate the degree to which the level of radioactive contamination affects the development of animals at Chornobyl. However, the mechanisms leading to these effects are not clear and probably vary from population to population. There were significant correlations between the overall right to left differences for the Procrustes aligned shape configurations, centroid sizes, and intramuscular (137)Cs. Detectable effects of radiation on developmental stability probably start to occur between 0.132 and 0.297 microGy/h.

Animals↗

KASER: Knowledge Amplification by Structured Expert Randomization.

In this paper and attached video, we present a third-generation expert system named Knowledge Amplification by Structured Expert Randomization (KASER) for which a patent has been filed by the U.S. Navy's SPAWAR Systems Center, San Diego, CA (SSC SD). KASER is a creative expert system. It is capable of deductive, inductive, and mixed derivations. Its qualitative creativity is realized by using a tree-search mechanism. The system achieves creative reasoning by using a declarative representation of knowledge consisting of object trees and inheritance. KASER computes with words and phrases. It possesses a capability for metaphor-based explanations. This capability is useful in explaining its creative suggestions and serves to augment the capabilities provided by the explanation subsystems of conventional expert systems. KASER also exhibits an accelerated capability to learn. However, this capability depends on the particulars of the selected application domain. For example, application domains such as the game of chess exhibit a high degree of geometric symmetry. Conversely, application domains such as the game of craps played with two dice exhibit no predictable pattern, unless the dice are loaded. More generally, we say that domains whose informative content can be compressed to a significant degree without loss (or with relatively little loss) are symmetric. Incompressible domains are said to be asymmetric or random. The measure of symmetry plus the measure of randomness must always sum to unity.

Algorithms↗

Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults.

Resiquimod is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent inducer of alpha interferon (IFN-alpha) and other cytokines. The effects of multiple applications of resiquimod gel were assessed in a randomized, single-blind, dose-ranging, placebo-controlled study with 41 healthy subjects. Over a 3-week period, 1-g doses of resiquimod or vehicle gel (3:1 randomization) were applied to a 50-cm2 area of the upper arm according to the following regimens: 0.25% applied for 8 h two times per week, 0.05% applied for 8 h two times per week, 0.05% applied for 8 h three times per week, and 0.01% applied for 24 h three times per week. Skin biopsy specimens were obtained prior to the application of the first dose and after the completion of application of the last dose. Dosing with 0.01 and 0.05% resiquimod was well tolerated, but that with 0.25% was not; a dose-response relationship for local adverse effects was observed. The level of systemic exposure during multiple topical dosings was <1% of the applied dose. A significant increase in responders after completion of application of the last dose was observed for serum IFN and the interleukin-1 (IL-1) receptor antagonist (P<0.01, Fisher's exact test). Increased levels of mRNA for IL-6, IL-8, IFN-alpha, and Mx (an IFN-alpha-inducible protein) were seen in posttreatment biopsy specimens from the group receiving 0.25% resiquimod compared to the levels seen in specimens from the group receiving vehicle only (P<0.01, Wilcoxon rank sum test). A dose-response-related increase in CD3-positive cells consistent with T-lymphocyte infiltration and a decrease in CD1a-positive cells, consistent with emigration of Langerhans' cells, were observed in treated skin. This study suggests that resiquimod is a potent topically active immune response modifier that significantly enhances the cutaneous immune response.

Adjuvants, Immunologic↗

Ecological half-life of 137Cs in plants associated with a contaminated stream.

Ecological half-life (Te) is a useful measure for studying the long-term decline of contaminants, such as radionuclides, in natural systems. The current investigation determined levels of radiocesium (137Cs) in two aquatic (Polygonum punctatum, Sagittaria latifolia) and three terrestrial (Alnus serrulata, Myrica cerifera, Salix nigra) plant species from a contaminated stream and floodplain on the U.S. Department of Energy's Savannah River Site. Current 137Cs levels in plants were used in conjunction with historical data to determine Te of 137Cs in each species. Median concentrations of 137Cs were highest in S. latifolia (0.84 Bq g(-1)) and lowest in M. cerifera (0.10 Bq g(-1)). Te's ranged from 4.85 yr in M. cerifera to 8.35 yr in S. nigra, both terrestrial species. Te's for all aquatic (6.30 yr) and all terrestrial (5.87) species combined were very similar. The Te's of the two aquatic primary producers (P. punctatum and S. latifolia) in the Steel Creek ecosystem were somewhat longer than Te values previously reported for some consumers from this ecosystem.

Cesium Radioisotopes↗

Frequency distributions of 137Cs in fish and mammal populations.

We collected fish and mammals in several radioactively contaminated locations in the Chornobyl Exclusion Zone and analyzed them for 137Cs content. Frequency distributions were built for populations of channel catfish, yellow-necked mice and bank voles. We combined our data with similar data from several other studies to demonstrate the relationship between the standard deviations and means of 137Cs of fish and mammal populations. The frequency distributions of 137Cs in populations of fish and mammals are not normal, as indicated by the strong relationship between standard deviation and mean. Distributions for mammals are more skewed than those for fish. Fish and mammals probably use their environments in fundamentally different ways. The highest concentrations and thus greatest risks are therefore confined to relatively few individuals in each population.

Animals↗